Background In the United States, e-cigarettes, or vapes, are the second most commonly used tobacco product. Despite abundant smartphone app–based cigarette cessation programs, there are few such programs for vaping and even fewer supporting data. Objective This exploratory, prospective, single-arm, remote cohort study of the Pivot vaping cessation program assessed enrollment and questionnaire completion rates, participant engagement and retention, changes in attitudes toward quitting vaping, changes in vaping behavior, and participant feedback. We aimed to establish early data to inform program improvements and future study design. Methods American adults aged ≥21 years who vaped daily, reported ≥5 vape sessions per day, and planned to quit vaping within 6 months were recruited on the web. Data were self-reported via app- and web-based questionnaires. Outcomes included engagement and retention (ie, weeks in the program, number of Pivot app openings, and number of messages sent to the coach), vaping attitudes (ie, success in quitting and difficulty staying quit), vaping behavior (ie, quit attempts, Penn State Electronic Cigarette Dependence Index, 7- and 30-day point-prevalence abstinence [PPA], and continuous abstinence [defined as ≥7-day PPA at 12 weeks+30-day PPA at 26 weeks+0 vaping sessions since 12 weeks]), and participant feedback. Results In total, 73 participants onboarded (intention-to-treat sample); 68 (93%) completed the 12- and 26-week questionnaires (completer samples). On average, participants were active in Pivot for 13.8 (SD 7.3) weeks, had 87.3 (SD 99.9) app sessions, and sent 37.6 (SD 42.3) messages to their coach over 26 weeks. Mean success in quitting and difficulty staying quit (scale of 1-10) improved from baseline to 12 weeks—4.9 (SD 2.9) to 7.0 (SD 3.0) and 4.0 (SD 2.8) to 6.2 (SD 3.1), respectively (P<.001 in both cases). Most participants (64/73, 88%) made ≥1 quit attempt. At 26 weeks, intention-to-treat 7-day PPA, 30-day PPA, and continuous abstinence rates were 48% (35/73), 45% (33/73), and 30% (22/73), respectively. In total, 45% (33/73) of the participants did not achieve 7-day PPA at 26 weeks; their mean Penn State Electronic Cigarette Dependence Index score decreased from baseline (13.9, SD 3.1) to 26 weeks (10.8, SD 4.5; mean change –3.2, SD 3.9; P<.001); 48% (16/33) of these participants improved in the e-cigarette dependence category. At 2 weeks, 72% (51/71) of respondents reported that using Pivot increased their motivation to quit vaping; at 4 weeks, 79% (55/70) reported using Pivot decreased the amount they vaped per day. Conclusions In this first evaluation of Pivot in adult daily vapers, questionnaire completion rates were >90%, average program engagement duration was approximately 14 weeks, and most participants reported increased motivation to quit vaping. These and early cessation outcomes herein suggest a role for Pivot in vaping cessation and will inform associated future study and program improvements.

Abstract BACKGROUND Growth failure impacts 15-40% of children with Crohn’s disease (CD). Potential causes of growth failure include chronic inflammation, malabsorption, and poor nutritional intake. Control of inflammation is key to improving growth outcomes. Anti-TNF therapy has been associated with improved growth and nutritional status in affected children. Large studies of serial outcomes of growth after anti-TNF therapy initiation are limited. OBJECTIVE We sought to 1) describe baseline weight, height, and BMI status at anti-TNF initiation in children with CD in a large, multicenter clinical trial, 2) compare the demographic and clinical characteristics of children with and without weight, height, and BMI disturbance, and 3) describe follow-up anthropometric parameters at approximately 12 and 24 months after anti-TNF initiation. METHODS We analyzed data from the COMBINE trial, a multicenter study comparing infliximab or adalimumab in combination with oral methotrexate to anti-TNF monotherapy for children with CD. We obtained demographic, clinical, and anthropometric data at time of enrollment and after 12 and 24 months. Weight, height, and BMI Z-scores were dichotomized as normal (≥ -1) versus disturbance (< -1) at each time point. We used standard descriptive statistics to summarize the distribution of Z-scores and bivariate statistics to compare demographic, clinical, and treatment characteristics among participants with versus without growth disturbance at baseline. RESULTS Our study population included 199 children (25% female, 83% white, mean age 12 years). Of these, 53 (26.6%) had a weight disturbance at baseline (Table 1). Of 188 children with height data available at baseline, 52 (27.7%) had a height disturbance and 37 (19.7%) had a BMI disturbance. The mean short pediatric CD activity index (sPCDAI) was higher in those defined with weight, height, and BMI disturbance at baseline compared to those with normal parameters (Table 2). Gender, race, ethnicity, and age at time of anti-TNF initiation were not different between groups with and without weight, height, or BMI disturbances. Approximately 12 months after enrollment, the proportion of patients with height disturbance was 6.1% with a continued decrease to 0.9% at 24 months. BMI disturbance was observed in 7.5% of participants at 12 months and 2.8% at 24 months. Weight disturbance was observed among 5.7% and 0.8% of participants at 12 and 24 months respectively. DISCUSSION A substantial proportion of children with CD had weight, height, and BMI disturbance at time of anti-TNF initiation. These proportions decreased at approximately 12 months and 24 months, demonstrating significant improvement in growth disturbances after anti-TNF therapy. Table 1 % of children with weight, height, and BMI disturbance (Z-score <-1) at time of enrollment in addition to 12 and 24 months after anti-TNF therapy initiation. Table 2 Mean short pediatric Crohn’s disease activity index (sPCDAI) for BMI, weight, and height at time of anti-TNF initiation.

Background: Higher drug levels and combination therapy with low-dose oral methotrexate (LD-MTX) may reduce anti-tumor necrosis factor (TNF) treatment failure in pediatric Crohn's disease. We sought to (1) evaluate whether combination therapy with LD-MTX was associated with higher anti-TNF levels, (2) evaluate associations between anti-TNF levels and subsequent treatment failure, and (3) explore the effect of combination therapy on maintenance of remission among patients with therapeutic drug levels (>5 mu g/mL for infliximab and >7.5 mu g/mL for adalimumab). Methods: We conducted a post hoc analysis of the COMBINE trial, which compared anti-TNF monotherapy to combination therapy with LD-MTX. We included participants who entered maintenance therapy and provided a serum sample approximately 4 months from randomization. Results: Among 112 infliximab and 41 adalimumab initiators, median drug levels were similar between combination therapy and monotherapy (infliximab: 8.8 vs 7.5 mu g/mL [P = .49]; adalimumab: 11.1 vs 10.5 mu g/mL [P = .11]). Median drug levels were lower in patients experiencing treatment failure (infliximab: 4.2 vs 9.6 mu g/mL [P < .01]; adalimumab: 9.1 vs 12.3 mu g/mL [P < .01]). Among patients treated with infliximab with therapeutic drug levels, we observed no difference in treatment failure between participants assigned monotherapy or combination therapy. Among patients treated with adalimumab, a trend towards reduced treatment failure in the combination therapy arm was not statistically significant (P = .14). Conclusions: LD-MTX combination was not associated with higher drug levels, but higher drug levels were associated with reduced risk of treatment failure. Among patients with therapeutic drug levels, we observed no benefit of LD-MTX for patients treated with infliximab. A nonsignificant trend towards reduced treatment failure with the addition of LD-MTX patients treated with adalimumab warrants further investigation.

OBJECTIVES:HLA DQA1*05 has been associated with the development of anti-drug antibodies (ADA) to tumor necrosis factor antagonists (anti-TNF) and treatment failure among adults with Crohn's disease (CD). However, findings from other studies have been inconsistent with limited pediatric data. METHODS:We analyzed banked serum from patients with CD < 21 years of age enrolled in COMBINE, a multi-center, prospective randomized trial of anti-TNF monotherapy vs. combination with methotrexate. The primary outcome was a composite of factors indicative of treatment failure. The secondary outcome was ADA development. RESULTS:A trend towards increased treatment failure among HLA DQA1*05 positive participants was not significant (HR 1.58, 95% CI 0.95-2.62; p=0.08). After stratification by HLA DQA1*05 and by methotrexate vs. placebo, patients who were HLA DQA1*05 negative and assigned to methotrexate experienced less treatment failures than HLA DQA1*05 positive patients on placebo (HR 0.31, 95% CI 0.13-0.70; p=0.005).A trend toward increased ADA development among HLA DQA1*05 positive participants was not significant (odds ratio [OR] 1.96, 95% CI 0.90-4.31, p=0.09). After further stratification, HLA DQA1*05 negative participants assigned to methotrexate were less likely to develop ADA relative to HLA DQA1*05 positive patients on placebo (OR 0.12, 95% CI 0.03-0.55; p=0.008). CONCLUSIONS:In a randomized trial of children with CD initiating anti-TNF, 40% were HLA DQ-A1*05 positive, which was associated with a trend toward increased risk of both treatment failure and ADA. These risks were mitigated, but not eliminated, by adding oral methotrexate. HLA DQ-A1*05 is an important biomarker for prognosis and risk stratification.

INTRODUCTION:Human leukocyte antigen (HLA) DQA1*05 has been associated with the development of anti-drug antibodies (ADA) to tumor necrosis factor antagonists (anti-TNFα) and treatment failure among adults with Crohn's disease (CD). However, findings from other studies have been inconsistent with limited pediatric data. METHODS:We analyzed banked serum from patients with CD aged <21 years enrolled in clinical outcomes of Methotrexate Binary Therapy in practice, a multicenter, prospective randomized trial of anti-TNFα monotherapy vs combination with methotrexate. The primary outcome was a composite of factors indicative of treatment failure. The secondary outcome was ADA development. RESULTS:A trend toward increased treatment failure among HLA DQA1*05-positive participants was not significant (hazard ratio 1.58, 95% confidence interval [CI] 0.95-2.62; P = 0.08). After stratification by HLA DQA1*05 and by methotrexate vs placebo, patients who were HLA DQA1*05 negative and assigned to methotrexate experienced less treatment failures than HLA DQA1*05-positive patients on placebo (hazard ratio 0.31, 95% CI 0.13-0.70; P = 0.005). A trend toward increased ADA development among HLA DQA1*05-positive participants was not significant (odds ratio 1.96, 95% CI 0.90-4.31, P = 0.09). After further stratification, HLA DQA1*05-negative participants assigned to methotrexate were less likely to develop ADA relative to HLA DQA1*05-positive patients on placebo (odds ratio 0.12, 95% CI 0.03-0.55; P = 0.008). DISCUSSION:In a randomized trial of children with CD initiating anti-TNFα, 40% were HLA DQ-A1*05 positive, which was associated with a trend toward increased risk of both treatment failure and ADA. These risks were mitigated, but not eliminated, by adding oral methotrexate. HLA DQ-A1*05 is an important biomarker for prognosis and risk stratification.

Objective We aimed to determine whether mepolizumab, an anti-IL- 5 antibody, was more effective than placebo for improving dysphagia symptoms and decreasing oesophageal eosinophil counts in eosinophilic oesophagitis (EoE). Methods We conducted a multicentre, randomised, double-blind, placebo-controlled, trial. In the first part, patients aged 16-75 with EoE and dysphagia symptoms (per EoE Symptom Activity Index (EEsAI)) were randomised 1:1 to 3 months of mepolizumab 300 mg monthly or placebo. Primary outcome was change in EEsAI from baseline to month 3 (M3). Secondary outcomes included histological, endoscopic and safety metrics. In part 2, patients initially randomised to mepolizumab continued 300 mg monthly for 3 additional months (mepo/mepo), placebo patients started mepolizumab 100 mg monthly (pbo/mepo), and outcomes were reassessed at month 6 (M6). Results Of 66 patients randomised, 64 completed M3, and 56 completed M6. At M3, EEsAI decreased 15.4 +/- 18.1 with mepolizumab and 8.3 +/- 18.0 with placebo (p=0.14). Peak eosinophil counts decreased more with mepolizumab (113 +/- 77 to 36 +/- 43) than placebo (146 +/- 94 to 160 +/- 133) (p<0.001). With mepolizumab, 42% and 34% achieved histological responses of <15 and =6 eos/hpf compared with 3% and 3% with placebo (p<0.001 and 0.02). The change in EoE Endoscopic Reference Score at M3 was also larger with mepolizumab. At M6, EEsAI decreased 18.3 +/- 18.1 points for mepo/mepo and 18.6 +/- 19.2 for pbo/mepo (p=0.85). The most common adverse events were injection-site reactions. Conclusions Mepolizumab did not achieve the primary endpoint of improving dysphagia symptoms compared with placebo. While eosinophil counts and endoscopic severity improved with mepolizumab at 3 months, longer treatment did not yield additional improvement.

BACKGROUND & AIMS:Tumor necrosis factor inhibitors, including infliximab and adalimumab, are a mainstay of pediatric Crohn's disease therapy; however, nonresponse and loss of response are common. As combination therapy with methotrexate may improve response, we performed a multicenter, randomized, double-blind, placebo-controlled pragmatic trial to compare tumor necrosis factor inhibitors with oral methotrexate to tumor necrosis factor inhibitor monotherapy.METHODS:Patients with pediatric Crohn's disease initiating infliximab or adalimumab were randomized in 1:1 allocation to methotrexate or placebo and followed for 12-36 months. The primary outcome was a composite indicator of treatment failure. Secondary outcomes included anti-drug antibodies and patient-reported outcomes of pain interference and fatigue. Adverse events (AEs) and serious AEs (SAEs) were collected.RESULTS:Of 297 participants (mean age, 13.9 years, 35% were female), 156 were assigned to methotrexate (110 infliximab initiators and 46 adalimumab initiators) and 141 to placebo (102 infliximab initiators and 39 adalimumab initiators). In the overall population, time to treatment failure did not differ by study arm (hazard ratio, 0.69; 95% CI, 0.45-1.05). Among infliximab initiators, there were no differences between combination and monotherapy (hazard ratio, 0.93; 95% CI, 0.55-1.56). Among adalimumab initiators, combination therapy was associated with longer time to treatment failure (hazard ratio, 0.40; 95% CI, 0.19-0.81). A trend toward lower anti-drug antibody development in the combination therapy arm was not significant (infliximab: odds ratio, 0.72; 95% CI, 0.49-1.07; adalimumab: odds ratio, 0.71; 95% CI, 0.24-2.07). No differences in patient-reported outcomes were observed. Combination therapy resulted in more AEs but fewer SAEs.CONCLUSIONS:Among adalimumab but not infliximab initiators, patients with pediatric Crohn's disease treated with methotrexate combination therapy experienced a 2-fold reduction in treatment failure with a tolerable safety profile.CLINICALTRIALS:gov, Number: NCT02772965.

INTRODUCTION: Patients with alpha-gal syndrome, a delayed reaction to mammalian meat, can present with isolated gastrointestinal (GI) symptoms. We aimed to estimate the frequency of alpha-gal sensitization in a Southeastern US population and determine the association between sensitization and mammalian product dietary intake or GI symptoms. METHODS: We performed a cross-sectional study of participants who underwent a screening colonoscopy at our center between 2013 and 2015. We quantified serum alpha-gal immunoglobulin E antibodies in participants who were prospectively enrolled at screening colonoscopy and compared diet intake and lower GI symptoms reported in standardized questionnaires among those with elevated versus no alpha-gal IgE antibodies. RESULTS: Alpha-gal IgE antibodies were common—31.4% of screening colonoscopy participants (127 of 404) had elevated serum alpha-gal IgE >0.1 kU/L. Alpha-gal–sensitized participants endorsed similar rates of abdominal pain compared with those without alpha-gal antibodies (33% vs 38%, adjusted odds ratio 0.9, 95% confidence interval 0.7–1.3). Mammalian meat consumption did not differ based on alpha-gal sensitization status (average 1.43 servings/d in sensitized subjects vs 1.50 in alpha-gal IgE–negative subjects, P = 0.9). Alpha-gal–sensitized participants with levels ≥10 (n = 21) were overrepresented in the lowest quartiles of mammalian meat consumption, but not among those with GI symptoms in general. Participants with high alpha-gal antibody levels >2 kU/L (n = 45) or ≥10 U/L (n = 21) did not have a reduced mean daily mammalian meat intake compared with seronegative people. DISCUSSION: Elevated alpha-gal IgE antibodies were common and not associated with a reduced mammalian meat intake, abdominal pain, or diarrhea. Seropositivity did not predict symptomatic alpha-gal sensitization in this general screening population. Other host factors likely contribute to the phenotypic expression of alpha-gal syndrome.

Supplementary Tables and Methods.

Hemorrhoids are a common but poorly understood gastrointestinal condition.1 Bowel habits and fiber consumption are frequently cited as risk factors for hemorrhoids, but research has been inconclusive.2 Recent genome-wide association studies (GWAS) have suggested an association between diverticular disease and hemorrhoids.3 We sought to investigate the association between colonic diverticulosis and internal hemorrhoids to validate the prediction from the GWAS.

Development of the inflammatory bowel diseases (IBD) has been linked to altered homeostatic relationships between the intestine and the microbiota it harbors. However early preclinical stages of IBD remain poorly understood, especially with respect to host-microbiota interactions. The nuclear receptor transcription factor Hepatocyte nuclear factor 4 alpha (HNF4A) has important roles in intestinal epithelial cell (IEC) physiology, and our recent studies in zebrafish and mice revealed that HNF4A activity in IEC is suppressed by intestinal microbiota. Variants at HNF4A have been associated with human IBD, and IEC-specific knockout of Hnf4a in mice ( Hnf4a ΔIEC ) leads to spontaneous colonic inflammation by 6-12 months. We hypothesized that intestinal pathology in Hnf4a ΔIEC mice may begin earlier in life and that microbiota may contribute to that process. Longitudinal analysis revealed that Hnf4a ΔIEC mice reared in specific pathogen-free (SPF) conditions develop fecal lipocalin 2 (LCN2) flares and episodic loose stools beginning as early as 4-5 weeks of age. Lifetime cumulative LCN2 levels correlated with histopathological features of colitis at 12 months of age. Antibiotic and gnotobiotic tests showed that these phenotypes in Hnf4a ΔIEC mice were dependent on the presence of microbiota. Fecal 16S rRNA gene sequencing in an SPF cohort of Hnf4a ΔIEC mice and controls at 12 months of age disclosed that genotype was a significant contributor to alterations in microbiota composition. Longitudinal analysis in a subset of inflamed Hnf4a ΔIEC and wild-type mice revealed that microbial community differences emerged at early life stages when fecal LCN2 flares first arose. These microbiota differences included a salient increase in the relative abundance of Akkermansia muciniphila in a subset of Hnf4a ΔIEC mice. We isolated an A. muciniphila strain from an aged, inflamed Hnf4a ΔIEC mouse, and its genome sequence revealed it to be a member of a new Akkermansia phylogroup with genetic features distinct from the known phylogroups. We conclude that HNF4A functions in IEC throughout the lifespan to protect against episodic flares of inflammation induced by microbiota while also shaping microbiota assembly. These results establish Hnf4a ΔIEC mice as a useful model for investigating preclinical pathology and host-microbiota interactions that precede overt IBD onset. NIH P01-DK094779 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The inflammatory bowel diseases (IBD) occur in genetically susceptible individuals who mount inappropriate immune responses to their microbiota leading to chronic intestinal inflammation. Whereas IBD clinical presentation is well described, how interactions between microbiota and host genotype impact early subclinical stages of the disease remains unclear. The transcription factor hepatocyte nuclear factor 4 alpha (HNF4A) has been associated with human IBD, and deletion of Hnf4a in intestinal epithelial cells (IECs) in mice (Hnf4aΔIEC) leads to spontaneous colonic inflammation by 6-12 mo of age. Here, we tested if pathology in Hnf4aΔIEC mice begins earlier in life and if microbiota contribute to that process. Longitudinal analysis revealed that Hnf4aΔIEC mice reared in specific pathogen-free (SPF) conditions develop episodic elevated fecal lipocalin 2 (Lcn2) and loose stools beginning by 4-5 wk of age. Lifetime cumulative Lcn2 levels correlated with histopathological features of colitis at 12 mo. Antibiotic and gnotobiotic tests showed that these phenotypes in Hnf4aΔIEC mice were dependent on microbiota. Fecal 16S rRNA gene sequencing in SPF Hnf4aΔIEC and control mice disclosed that genotype significantly contributed to differences in microbiota composition by 12 mo, and longitudinal analysis of the Hnf4aΔIEC mice with the highest lifetime cumulative Lcn2 revealed that microbial community differences emerged early in life when elevated fecal Lcn2 was first detected. These microbiota differences included enrichment of a novel phylogroup of Akkermansia muciniphila in Hnf4aΔIEC mice. We conclude that HNF4A functions in IEC to shape composition of the gut microbiota and protect against episodic inflammation induced by microbiota throughout the lifespan. IMPORTANCE The inflammatory bowel diseases (IBD), characterized by chronic inflammation of the intestine, affect millions of people around the world. Although significant advances have been made in the clinical management of IBD, the early subclinical stages of IBD are not well defined and are difficult to study in humans. This work explores the subclinical stages of disease in mice lacking the IBD-associated transcription factor HNF4A in the intestinal epithelium. Whereas these mice do not develop overt disease until late in adulthood, we find that they display episodic intestinal inflammation, loose stools, and microbiota changes beginning in very early life stages. Using germ-free and antibiotic-treatment experiments, we reveal that intestinal inflammation in these mice was dependent on the presence of microbiota. These results suggest that interactions between host genotype and microbiota can drive early subclinical pathologies that precede the overt onset of IBD and describe a mouse model to explore those important processes.

INTRODUCTION: Microscopic colitis, a common cause of diarrhea, is characterized by a largely normal appearance of the mucosa but increased numbers of lymphocytes in the epithelium and lamina propria on microscopy. We sought to determine whether T-cell percentage was associated with exposures or symptoms. METHODS: We conducted a case-control study that enrolled patients referred for colonoscopy for diarrhea. Patients were classified as microscopic colitis cases or controls by an experienced pathologist. Participants provided information on symptoms and exposures during a telephone or internet survey. Research biopsies from the ascending colon and descending colon were examined using immunofluorescence stains for CD3, CD8, and FOXP3 to determine percent T cells per total epithelial or lamina propria cells. Digital images were analyzed by regions of interest using Tissue Studio. RESULTS: There were 97 microscopic colitis cases and 165 diarrhea controls. There was no association between demographic factors and percentage of intraepithelial or lamina propria T cells. In cases, the mean percent T cells were similar in the right colon and left colon. There was no association between mean percent T cells and stool frequency or consistency. There was no association with irritable bowel syndrome, abdominal pain, or medications purported to cause microscopic colitis. DISCUSSION: The lack of association between the density of T cells and medications raises further doubts about their role in disease etiology. Loose and frequent stools in patients with microscopic colitis are not correlated with T-cell density.

Abstract ECT2 is an activator of RHO GTPases that is essential for cytokinesis. In addition, ECT2 was identified as an oncoprotein when expressed ectopically in NIH/3T3 fibroblasts. However, oncogenic activation of ECT2 resulted from N-terminal truncation, and such truncated ECT2 proteins have not been found in patients with cancer. In this study, we observed elevated expression of full-length ECT2 protein in preneoplastic colon adenomas, driven by increased ECT2 mRNA abundance and associated with APC tumor-suppressor loss. Elevated ECT2 levels were detected in the cytoplasm and nucleus of colorectal cancer tissue, suggesting cytoplasmic mislocalization as one mechanism of early oncogenic ECT2 activation. Importantly, elevated nuclear ECT2 correlated with poorly differentiated tumors, and a low cytoplasmic:nuclear ratio of ECT2 protein correlated with poor patient survival, suggesting that nuclear and cytoplasmic ECT2 play distinct roles in colorectal cancer. Depletion of ECT2 reduced anchorage-independent cancer cell growth and invasion independent of its function in cytokinesis, and loss of Ect2 extended survival in a KrasG12D Apc-null colon cancer mouse model. Expression of ECT2 variants with impaired nuclear localization or guanine nucleotide exchange catalytic activity failed to restore cancer cell growth or invasion, indicating that active, nuclear ECT2 is required to support tumor progression. Nuclear ECT2 promoted ribosomal DNA transcription and ribosome biogenesis in colorectal cancer. These results support a driver role for both cytoplasmic and nuclear ECT2 overexpression in colorectal cancer and emphasize the critical role of precise subcellular localization in dictating ECT2 function in neoplastic cells. Significance: ECT2 overexpression and mislocalization support its role as a driver in colon cancer that is independent from its function in normal cell cytokinesis.

BACKGROUND AND AIMS:Symptomatic uncomplicated diverticular disease is a controversial diagnosis defined as chronic gastrointestinal symptoms in patients with diverticulosis. We assessed whether individuals with diverticulosis had an increased risk of abdominal pain, irritable bowel syndrome, or altered bowel habits. METHODS:We performed a prospective cohort study of participants who had a first-time screening colonoscopy at the University of North Carolina between 2013 and 2015. The colonoscopy included a detailed assessment for diverticulosis. Participants completed a follow-up interview between 2019 and 2020 to measure bowel habits and gastrointestinal symptoms. Poisson regression was used to estimate relative risk and 95% confidence intervals (CIs). RESULTS:Among the 310 participants, 128 (41%) had diverticulosis at baseline. Follow-up interviews were performed a mean of 6.8 years after the baseline colonoscopy. After adjustment for confounders, there was no association between diverticulosis and abdominal pain lasting >24 hours (relative risk [RR], 0.40; 95% CI, 0.05-3.45) or symptoms of irritable bowel syndrome (RR, 1.30; 95% CI, 0.69-2.42) at the time of follow-up. Compared to those with no diverticulosis, participants with diverticulosis were more likely to have more frequent bowel movements per day (RR, 1.60; 95% CI, 1.05-2.44). The association was stronger in participants with >10 diverticula (RR, 2.03; 95% CI, 1.19-3.48). Diverticulosis was not associated with altered stool consistency. CONCLUSION:These findings suggest that diverticulosis is associated with more frequent bowel movements contrary to the widespread belief that patients with diverticulosis are constipated. Diverticulosis was not associated with abdominal pain or symptoms of irritable bowel syndrome. The diagnosis of symptomatic uncomplicated diverticular disease must be reconsidered.

Background: Research on the utilization and effectiveness of antitumor necrosis factor (TNF) biologics in children with very early onset inflammatory bowel disease (VEOIBD) is urgently needed. Here we describe anti-TNF use and durability in a multicenter cohort. Methods: We performed a retrospective cohort study of patients diagnosed with VEOIBD (<6 years) between 2008 and 2013 at 25 North American centers. We performed chart abstraction at diagnosis and 1, 3, and 5 years after diagnosis. We examined the rate of initiation and durability of infliximab and adalimumab and evaluated associations between treatment durability and the following covariates with multivariate Cox proportional hazard regression: age at diagnosis, sex, disease duration, disease classification, and presence of combined immunomodulatory treatment versus monotherapy. Results: Of 294 children with VEOIBD, 120 initiated treatment with anti-TNF therapy and 101 had follow-up data recorded [50% Crohn disease (CD), 31% ulcerative colitis (UC), and 19% IBD unclassified (IBD-U)]. The cumulative probability of anti-TNF treatment was 15% at 1 year, 30% at 3 years, and 45% at 5 years from diagnosis; 56 (55%) were treated between 0 and 6 years old. Anti-TNF durability was 90% at 1 year, 75% at 3 years, and 55% at 5 years. The most common reason for discontinuation of anti-TNF were loss of response in 24 (57%) children. Children with UC/IBD-U had lower durability than those with CD (hazard ratio [HR] 0.17; 95% confidence interval [CI], 0.06–0.51; P = 0.001). Conclusions: Utilization and durability of anti-TNF in VEOIBD is relatively high and comparable with older children. Having Crohn disease (compared with UC/IBD-U) is associated with greater durability.